Cancer has become a serious threat to human health. Researchers are pursuing effective, safe, and low-toxicity small molecular anti-tumor drugs. With the development of medicinal chemistry, research on natural products with anti-tumor activities and the derivatives of these products became an important trend.
Lappaconitine ((1α, 14α, 16β)-20-ethyl-1,14,16-trimethoxycephin-4,8,9-triol 4-[2-(acetylamino)]benzoate, formula (II)) is an alkaloid isolated from the roots of Aconitumsinomotanum Nakai. (Advanced Chinese Plant Illustration, Vol. I, Institute of Botany, Chinese Academy of Sciences, Science Press, Beijing, 1992, page 688). Pharmacological experiments show that lappaconitine has a strong central analgesic effect, antipyretic, and local anesthesia effect. Toxicity experiments show that lappaconitine has no damage to the various organizations and no teratogenic effect.

Cinnamic acid is a natural aromatic fatty acid that is widely found in propolis, coffee, fruit and wine. Cinnamic acid has a wide range of pharmacological properties, such as anti-cancer, anti-oxidation, and antibacterial.
Recently, nitrogen-containing heterocyclic compounds and their derivatives have been used in the fields of medicine, pesticide and fuel. In pharmaceuticals, nitrogen-containing heterocyclic compounds are widely used, from penicillin to the present fourth-generation cephalosporins, antihypertensive drugs reserpine, pyrimidine antagonists antitumor with activity, barbiturates sedative hypnotic drugs, and synthetic analgesic drugs.
Cinnamic acid, aza-cinnamic acid and their derivatives have antitumor activities. As one new drug research and development strategy, they can be used as lead compounds for further research to obtain candidate compounds with better efficacy. One example is histone deacetylase inhibitor (HDI) inhibitor, Chidamide (approved in 2014), which was inspired by the introduction of aza-cinnamic acid and its derivatives in the compound design.
There remains a need for effective and safe small molecular anti-tumor drugs. There is also no report of lappaconitine aza-cinnamic acid derivatives.